Stop lung cancer progression at the earliest stage

Background

Squamous cell carcinoma (SCC) of the lung accounts for around 30% of lung cancer cases. It is difficult to detect early and even CT screening tends to miss early SCC lesions unlike adenocarcinomas, which appear as small nodules.

SCC of the lung progresses through grades of pre-cancerous lesions of increasing severity, eventually in some cases forming lung cancers.

At UCLH, Professor Sam Janes and Dr Jeremy George have established over the last twelve years, a cohort of over 120 patients in which they have monitored pre-cancerous lung lesions of varying severity.

In this cohort and patients in general, there are more pre-cancerous lesions than we would expect from the number of cancers, which suggests that not all these pre-cancerous lesions inevitably develop into carcinoma.

Using this unique group of patients and biopsy samples that we have taken from their airways we have identified what may be crucial changes to cell protein levels that occur just before a precancerous lesion becomes a cancer.

We will focus on two key changes in the expression of two genes that we think are important and could conceivably lead to novel therapies to stop lesions progressing:

• Matrix metallopeptidase 12 (MMP12), and
• LIM domain 7 (LMO7).

From what is already know about these genes and the clear change that we see in lesions that progress compared to those that disappear we aim to intensively investigate the roles of MMP12 and LMO7 in SCC progression and use this information to develop new strategies of early detection and possibly chemoprevention.

By understanding the changes involved in lung cancer development we will be able to devise strategies for early detection, prediction of lesion progression and novel eradication treatments.

Dr. Teixeira, University College London

What is the problem to be addressed?

Lung diseases, including chronic obstructive pulmonary disease and cancer, account for more than 10% of UK deaths and lung cancer remains the most lethal cancer type worldwide.

Lung cancer needs to be detected and treated earlier if we are to save lives. To do this we need to understand the changes to cell processes that converts normal lung airway cells (or epithelium) to a pre-cancerous epithelium (called pre-invasive lesions) and most importantly into a full-blown cancer.

By understanding the changes involved in lung cancer development we will be able to devise strategies for early detection, prediction of lesion progression and novel eradication treatments.

Expected findings and potential impact

After significant local investment, we now have the skills and technology to examine the crucial role of these two genes/proteins in the development of SCC.

We will understand how these proteins regulate lung cancer progression. We expect to prove that MMP12 and LMO7 are the key genes involved in SSC progression and that they can be targeted in the future to stop lung cancers forming.

We expect to generate data that will allow us to use MMP12 and LMO7 as a biological marker of cancer risk (or biomarker) that will allow accurate prediction of whether lesions will eventually progress into squamous cell carcinoma.

In addition, it is anticipated that we will identify mechanisms/pathways through which MMP12 and LMO7 protein interactions regulate lung SCC progression and this can be used for an early interventional therapy.

Lead researchers: Dr Vitor Teixeira | Location: University College London | Type of research: Early detection